PPARγ对大鼠心肌缺血/再灌注后恶性心律失常的影响

Effects of PPARγ on malignant arrhythmia in myocardial ischemia/reperfusion model rats

目的探讨大鼠心肌过氧化物酶体增殖物激活受体(PPAR)γ对缺血/再灌注(I/R)后恶性心律失常的影响。方法 24只SD大鼠随机分为4组:假手术组(Sham组),缺血/再灌注组(I/R组),罗格列酮+缺血/再灌注组(ROS组),PPARγ抑制剂GW9662+缺血/再灌注组(GW组),每组6只。采用冠状动脉左前降支结扎法制造I/R动物模型,缺血30 min,再灌注2 h。全程肢体Ⅱ导联心电图观察各组恶性心律失常发生次数并记录校正QT间期(QTc)的变化,RT-PCR检测PPARγm RNA表达。结果 ROS组发生5例恶性心律失常,I/R组2例,GW组1例,Sham组0例。ROS组的QTc间期在再灌注期较其他3组延长(均P<0.05),与I/R组和ROS组相比,GW组的QTc间期在缺血30 min及再灌注过程中缩短(均P<0.05)。与Sham组相比,其他3组PPAR-γm RNA表达明显升高(均P<0.05),ROS组PPARγm RNA表达水平最高,GW组较I/R组和ROS组表达下调(均P<0.05)。结论 PPARγ过表达可能导致心肌I/R恶性心律失常的发生。

Objective To investigate the effects of peroxisome proliferator activated receptor gamma（PPARγ） on ma-lignant arrhythmia in myocardial of ischemia/reperfusion（I/R） rats.Methods Twenty-four SD rats were randomly dividedinto four groups：Sham group,I/R group,rosiglitazone（ROS） group and PPARγ inhibitor GW9662（GW） group.The myocar-dial I/R injury was induced by ligation of the left anterior descending coronary artery,with ischemia for 30 min and reperfu-sion for 2 h.The whole process limb Ⅱ lead electrocardiogram was applied to observe the frequency of malignant arrhythmiaand record the corrected changes of QT（QTc） interval.RT-PCR was used to detect the expression of PPARγ m RNA.Results There were 5 cases of malignant arrhythmia in ROS group,2 in I/R and 1 in GW group,0 was found in Sham group.There was a prolongation of the QTc interval in ROS group than the other groups after ischemic stage（P〈0.05）.Comparedwith I/R group and ROS group,the QTc intervals were shorten in ischemia 30 min and reperfusion process in GW group（P〈0.05）.Compared with sham group,the expression of PPARγ m RNA was significantly increased in other three groups（P〈0.05）.The expression level of PPARγ m RNA was the highest in ROS group.The expression level of PPARγ m RNA was re-duced in GW group compared with that of I/R group and ROS group（P〈0.05）.Conclusion Over expression of PPARγmay lead to the occurrence of malignant arrhythmia in myocardial ischemia/reperfusion rats.